Ubiquitin C-terminal hydrolase (UCH-L1), also called neuronal-specific protein gene product (PGP9.3), is highly abundant in neurons. Generally, UCH enzymes are small, since there is only a proteolytic core domain that functions to cleave small molecular weight adducts from the ubiquitin C terminus (1). There are at least three mammalian isozymes which are tissue specific and developmentally regulated (UCH-L1, L2, L3). A handful of studies suggest that UCH-L1 could serve as a novel biomarker, which has the potential to determine injury severity in TBI patients (2). Four UCH active site residues, Gln84, Cys90, His166 and Asp181 (Yuh1) were identified previously through mutagenesis of UCH-L1 and determination of the crystal structure of UCH-L3 (3).

1. Larsen, C.N., Krantz, B.A. and Wilkinson, K.D. (1998). Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry, 37, 3358-3368. PMID: 9521656

2. Papa, L., Akinyi, L., Liu, M.C., Pineda, J.A., Tepas, J.J., 3rd, Oli, M.W., Zheng, W., Robinson, G., Robicsek, S.A., Gabrielli, A., Heaton, S. C., Hannay, H. J., Demery, J. A., Brophy, G. M., Layon, J., Robertson, C. S., Hayes, R. L., Wang, K. K. (2010). Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit. Care. Med., 38, 138-144. PMID: 19726976

3. Johnston, S.C., Riddle, S.M., Cohen, R.E. and Hill, C.P. (1999). Structural basis for the specificity of ubiquitin C-terminal hydrolases. EMBO J., 18, 3877-3887. PMID: 10406793